Seal structures for wet/dry automatic injectors

ABSTRACT

An automatic medicament injector having a compartment for a dry medicament component and a compartment for a wet medicament component. The two compartments are separated by a seal structure that converts from a sealing condition to a mixing condition when the device is activated. The seal structure includes a wiper that scrapes the interior walls in the dry component compartment to prevent the dry component from accumulating at the seal/glass interface. A tapered insert funnels the mixed medicament components to an attached needle assembly, but can be removed when the device is filled. A filter is provided between the medicament compartments and the needle assembly. A chamber between the filter and the needle allows for better flow through the filter. An actuation assembly drives the seal structure into the mixing condition and forces the mixed medicament through the needle and into the user.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a division of U.S. patent application Ser. No. 10/690,987, filedOct. 23, 2003, which is a continuation-in-part of U.S. patentapplication Ser. Nos. 09/897,422, filed Jul. 3, 2001, and 09/972,202,filed on Oct. 9, 2001, both of which claim priority to U.S. ProvisionalApplications Nos. 60/238,458, 60/238,448, and 60/238,447, all filed onOct. 10, 2000. The contents of all these applications are incorporatedby reference herein in their entireties.

BACKGROUND OF THE INVENTION

The invention relates to drug delivery devices. More particularly, theinvention relates to automatic injector assemblies capable of mixing twocomponents of a medicament and then delivering the mixed medicament toan injection site.

An automatic injector is a device that enables intramuscular (IM) orsubcutaneous administration of a dosage of medicament. Generally, themedicament is stored as a liquid formulation which is then injectedintramuscularly. An advantage of automatic injectors is that theycontain a measured dosage of a liquid medicament in a sealed sterilecartridge. As such, automatic injectors allow for quick and simple IMinjection of a liquid medicament in emergency situations without theneed for measuring dosages. Another advantage of automatic injectors isthat the administration of the medicament is accomplished without theuser initially seeing the hypodermic needle through which the medicamentis delivered, and without requiring the user to manually force theneedle into the patient. This is particularly advantageous when themedicament is being self-administered.

There are drawbacks associated with the long-term storage of medicamentin a liquid formulation. For instance, some medicaments are not stablein solution and thus have a shorter shelf life than their solidcounterparts. To address this concern, automatic injectors have beendeveloped which store the medicament in solid form and mix the solidmedicament with a liquid solution immediately prior to injection. Theseinjectors, disclosed for example in US Reissue Patent No. 35,986,entitled “Multiple Chamber Automatic Injector,” (the disclosure of whichis incorporated herein specifically by reference), however, require theuser of the injector to manually rupture a sealing member between thesolid and liquid components and then manually shake the injector body toexpedite dissolution of the solid component prior to injection. Thisincreases the time needed to administer a dose of the medicament.However, rapid delivery of the medicament is needed in many emergencymedical situations (e.g., nerve gas and chemical agent poisoning). Otherwet/dry injection devices have been expensive to manufacture or provideunsatisfactory mixing of components prior to injection. Therefore, thereis a need for a cost-effective automatic injector that stores medicamentin solid form that does not require manual premixing by the user.

SUMMARY OF THE INVENTION

One aspect of the invention relates to an automatic injection devicecontaining a pre-loaded charge of medicament for automaticallyself-administering the medicament upon actuation thereof. The automaticinjection device comprises a housing and a medicament chamber disposedin the housing. The medicament chamber includes a first compartmentcontaining a dry medicament portion and a second compartment containinga wet medicament portion to be mixed with the dry medicament portion. Aseal structure is provided between the first compartment and the secondcompartment. The seal structure is initially in a sealing condition thatmaintains the first compartment separate from the second compartment.The seal structure includes at least one flow path and an annular wiperportion disposed at the front end of the seal structure and positionedto movingly engage inner walls of the first compartment as the sealstructure is moved through the first compartment. The wiper portion isconfigured to direct dry medicament particles engaged with the innerwalls of the medicament chamber radially inwardly as the seal structuremoves through the first compartment. The seal structure is converted toa mixing condition as a result of activation of the device. Theautomatic injection device also includes a needle assembly and anactivation assembly. The activation assembly is carried by the housingand includes a stored energy source. Activation of the activationassembly releases the stored energy from the stored energy source,causing the seal structure to be converted from the sealing condition tothe mixing condition, and thereby causing or allowing the medicamentportions to be mixed and forced through the needle assembly.

Another aspect of the invention relates to an automatic injection devicecontaining a pre-loaded charge of medicament for automaticallyself-administering the medicament upon actuation thereof. The automaticinjection device comprises a housing and a medicament chamber disposedin the housing. The medicament chamber includes a first compartmentcontaining a first medicament portion, and a second compartmentcontaining a second medicament portion to be mixed with the firstmedicament portion. The device also includes a seal structure betweenthe first compartment and the second compartment. The seal structure isinitially in a sealing condition that maintains the first compartmentseparate from the second compartment, and is converted to a mixingcondition as a result of activation of the device. A needle assemblydispenses the medicament charge from the medicament chamber. The needleassembly has a rearward opening with a diameter that is less than adiameter of the medicament chamber. An insert is mounted in a forwardend of the medicament chamber adjacent the needle assembly. The insertdefines a tapering flow pathway that tapers radially inwardly as itextends axially forwardly. An activation assembly is carried by thehousing and includes a stored energy source. Activation of theactivation assembly releases the stored energy from the stored energysource, causing the seal structure to be converted from the sealingcondition to the mixing condition, and thereby causing or allowing thefirst and second medicament portions to be mixed, directed by the insertradially inwardly toward the rearward opening of the needle assembly,and forced through the needle assembly.

Yet another aspect of the invention relates to an automatic injectiondevice containing a pre-loaded charge of medicament for automaticallyself-administering the medicament upon actuation thereof. The automaticinjection device comprises a housing and a medicament chamber disposedin the housing. The medicament chamber includes a first compartmentcontaining a first medicament portion, and a second compartmentcontaining a second medicament portion to be mixed with the firstmedicament portion. The device also includes a seal structure betweenthe first compartment and the second compartment. The seal structure isinitially in a sealing condition that maintains the first compartmentseparate from the second compartment, and is converted to a mixingcondition as a result of activation of the device. A needle assemblydispenses the medicament charge from the medicament chamber. A filter ispositioned between the medicament chamber and the needle assembly. Theneedle assembly comprises a needle and a needle support for mounting theneedle to the medicament chamber. The needle support defines a needleassembly chamber having a rearward opening covered by the filter. Theneedle assembly chamber has an inner surface tapering radially inwardlyas it extends axially forwardly toward a rearward end of the needle. Thedevice also has an activation assembly carried by the housing thatincludes a stored energy source. Activation of the activation assemblyreleases the stored energy from the stored energy source, causing theseal structure to be converted from the sealing condition to the mixingcondition, and thereby causing or allowing the first and secondmedicament compounds to be mixed and forced through the needle assembly.

A further aspect of the invention relates to a method of filling anautomatic injection device. The method comprises filling a frontcompartment of a chamber within the automatic injection device with adry medicament compound from a front end of the chamber. The method alsocomprises filling a rear compartment of the chamber with a wetmedicament portion from a rear end of the chamber. The rear compartmentis separated from the front compartment by a seal structure. Finally,the method comprises sealing the rear compartment of the chamber,placing a tapered insert in the front end of the chamber, and attachinga needle assembly to the front end of the chamber. The tapered inserthas a tapered flow pathway which is tapered such that the diameterincreases as it extends rearwardly.

These and other aspects and advantages of the invention will bedescribed below.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be described in conjunction with the followingdrawing figures, in which like reference numerals designate likeelements, and in which:

FIG. 1 is a longitudinal cross-sectional view of a wet/dry automaticinjector assembly in accordance with an embodiment of the presentinvention;

FIGS. 2A-2B illustrate longitudinal cross-sectional views of needlesupport assemblies in accordance with certain embodiments of the presentinvention;

FIGS. 3A-3D illustrate cross-sectional side views of various cartridgeor chamber configurations and corresponding needle assembly optionsaccording to certain embodiments of the present invention;

FIG. 4 is an enlarged partial cross-sectional side view of a needleassembly/cartridge engagement according to another embodiment;

FIGS. 5A-5D illustrate cross-sectional side views of various embodimentsof a seal structure according to the present invention;

FIG. 6A is a longitudinal cross-sectional side view of a seal structurein accordance with another embodiment of the present invention, whereinthe movable sealing plug is in a closed sealing position blocking theflow of the liquid injection solution;

FIG. 6B is a longitudinal cross sectional side view of seal structuresimilar to 6A, but showing the movable sealing plug in an open by-passposition permitting the flow of the liquid injection solution;

FIG. 6C is a lateral cross sectional view of the seal structure of thepresent invention taken through the line 6C-6C in FIG. 6A;

FIG. 6D is a lateral cross sectional view of the seal structure of thepresent invention taken through the line 6D-6D in FIG. 6B;

FIG. 7 is a longitudinal cross-sectional view of a wet/dry automaticinjector cartridge or chamber configuration in accordance with anotherembodiment of the present invention;

FIGS. 8A and 8B are longitudinal cross sectional views of two additionalembodiments of seal structures in accordance with the present invention;

FIG. 9 is a longitudinal cross-sectional view of a chamber and needleassembly according to a further embodiment of the invention;

FIG. 10 is a perspective view of an outer sealing member in the chamberand needle assembly of FIG. 9;

FIG. 11 is a front elevational view of the outer sealing member of FIG.10;

FIG. 12 is a longitudinal sectional view of the outer sealing member ofFIG. 10, taken through Line 12-12 of FIG. 11;

FIG. 13 is a perspective view of a tapered insert in the chamber andneedle assembly of FIG. 9;

FIG. 14 is a front elevational view of the tapered insert of FIG. 13;

FIG. 15 is a longitudinal sectional view of the tapered insert in thechamber and needle assembly of FIG. 13, taken through Line 15-15 of FIG.14;

FIG. 16 is a longitudinal sectional view of a portion of the needleassembly of FIG. 9, illustrating a chamber behind the needle assemblyfilter; and

FIGS. 17A-17F are sectional and partially sectional views of a chamberillustrating a process for filling it with dry and liquid medicamentcomponents.

DETAILED DESCRIPTION

In the following description, the present invention is described inconnection with a push button type auto injector, whereby the userremoves an end cap assembly and presses a button to trigger theinjection process. The present invention, however, is not limited topush button type automatic injectors; rather, it is contemplated thatthe present invention may be incorporated into a nose activated autoinjector, as described for example in U.S. Pat. No. 5,354,286, thedisclosure of which is hereby incorporated herein by reference for suchteaching.

FIG. 1 is a longitudinal cross-sectional view of an automatic injectorassembly 10 in accordance with an embodiment of the present invention.The automatic injector assembly 10 includes a generally hollow tubularplastic housing 110. Generally, the housing 110 includes an injectionend 111 and an activation end 112, as shown in FIG. 1. In the embodimentshown, an actuator assembly 120 is inserted into the rearward end of thehousing 110. The actuator assembly 120 is received within the housing110 until flange 115 of a sleeve member 144 is captured within anannular groove 117 on the interior surface of housing 110. A removablesafety cap 130 is releasably secured to the actuator assembly 120.

The actuator assembly 120 may be of any conventional type as known inthe art, such as that disclosed in commonly assigned U.S. Pat. No.5,391,151 hereby incorporated by reference. The present inventionemploys a rear-end activating device, similar to that in theaforementioned U.S. Pat. No. 5,391,151, and is therefore only brieflydescribed herein. The actuator assembly 120 includes an activationbutton sleeve 132 having internal activation surfaces 134. Theactivation assembly further includes a plastic collet 122 with a splitrearward portion forming spring fingers 136 as known in the art. Thesafety cap 130 has a pin portion 138 that extends between the springfingers 136 so as to keep them spread apart when the injector is in astorage condition. The spring fingers 136 terminate in semi-conicalconfigurations including rearwardly facing sloping surfaces 139 andforwardly facing flat surfaces 142. The collet 122 is surrounded by acylindrical sleeve 144 having inwardly extending flange 146 at therearward end thereof. The collet 122 has a forward annular flange 148. Acoil spring 250 surrounds the collet 122 and is compressed between theflange 148 and flange 146. The collet flat surfaces 142 are retained inengagement with the rearwardly facing surfaces of the flange 146, andthus prevented from moving off of the flange surfaces by the pin 138when the injector is stored.

To activate the injector, the safety pin 130 is manually pulled off ofthe rear end of the injector, thus removing pin 138 from between thefingers 136. The activation button 132 can then be pushed inwardly, andas a result of the activation surfaces thereof, 134 engages the slopingsurfaces 139 of the spring fingers 136. This forces the spring fingers136 inwards toward one another and off of the retaining surfaces of theflange 146. The compressed spring 250 is then free to release the storedenergy therein to move the collet 122 forwardly under the force of thespring to affect an injection operation as will be described later inmore detail.

The actuator assembly 120 may be of any type known in the automaticinjector art that employs releasable stored energy. For example, ratherthan employing a spring, it may employ a charge of compressed gas.

Located within the interior of the housing 110 is a vial or chamber 150,preferably made of glass, for containing both a liquid injectionsolution and a dry medicament, or other types of medicament portions, asappropriate. The chamber 150 is preferably a hollow cylinder, with asmooth cylindrical inner surface. The liquid injection solution islocated within a wet portion or compartment 151 of the chamber 150. Thedry medicament is located within a dry portion 152 or compartment of thechamber 150. It is contemplated that the dry medicament may be inpowder, lyophilized, freeze-dried, or any other solid formulation knownin the art. A seal structure 160 engages the interior side walls of thechamber 150 to seal the dry portion 152 from the wet portion 151 and toprevent seepage of the liquid injection solution into the dry portion152 prior to activation of the injector assembly. Further, a needleassembly 140 mounts to the forward end of vial or chamber 150 to injectthe medicament upon activation of the injector assembly. In thisembodiment, the forward end portion of the chamber 150 has an annulargroove 153 formed therein for attachment of the needle assembly 140. Theneedle assembly 140 includes a funnel-shaped needle support 143. Thewide end of the needle support 143 has an annular rib 145 that issnap-fit into groove 153 to form a seal with the chamber 150. The needlesupport 143 can be made of a resilient plastic material, or metal with arubber seal that seats into groove 153. The forward narrow end 147 (seeFIG. 2A) of the needle support 143 sealingly receives the rearward endof hollow needle 141. The needle support 143 forms a sealed fluidchannel from the chamber 150 to the needle 141. A rubber needle sheath202 surrounds the needle 141 and receives the narrow end 147 of theneedle support 143. A filter 190 is sealingly retained across the entirewide-end mouth of the needle support 143 by an annular sealing washer156. Alternatively, the filter 190 could be ultrasonically welded orotherwise secured to the needle support 143.

FIGS. 2B, 3A, and 4 illustrate another embodiment of a needle assembly140 and chamber 150. The chamber 150 in this embodiment is known in theart as a dental cartridge. The dental cartridge has a cylindrical rearportion and a narrowed forward neck portion defining an outer annulargroove 153. The forward end of the dental cartridge defines an annularflange portion 154. In this embodiment, the needle support 143 has arearward annular flange 155 that receives an annular sealing member 156that surrounds both sides of flange 155. The sealing member 156 servesto seal a filter 190 over the wide end of the funnel shaped needlesupport 143. The rearward surface of the sealing member 156 is sealinglyclamped against the forward surface of chamber flange 154 by a metalretaining clamp 157 as best seen in FIG. 4.

As shown in FIG. 1, forward end 1221 of the collet 122 extends into therearward end of chamber 150 and is adapted to connect with a plunger 170rearwardly sealing the wet container 151. The plunger 170 is adapted tosealingly engage the side wall of the wet container 150 to preventleakage of the contents (e.g., liquid injection solution) of the wetcontainer 151. The plunger 170 is preferably formed from a materialhaving low frictional properties such that the collet 122 and plunger170 may easily slide within the wet container 150 when operated.Alternatively, the plunger 170 may be lubricated with silicone or othersuitable non-reactive lubricant. The movement of the collet 122 and theplunger 170 pressurizes the liquid located within the wet container 151.A suitable medicament is located within a dry container 152.

The embodiment of FIGS. 1 and 2A is advantageous in that it has an openmouth configuration wherein the needle-end of the vial or chamber is notsignificantly narrowed or tapered. Such an open mouth configurationpermits direct access to the dry portion 152 of chamber 150 for easyloading. Further, the open mouth configuration aids in preventing crosscontamination between wet portion 151 and dry portion 152 in that thedry portion 152 does not have to be filled through liquid portion 151 ofchamber 150. Needle assembly 140 can be mounted to vial or chamber 150in a snap-on configuration (FIG. 3B), an internal mount configuration(FIG. 3C), or an external needle assembly configuration (FIG. 3D).

As mentioned above, the seal structure 160 is adapted to engage theinterior side walls of chamber 150 to prevent passage of the contents(e.g., liquid injection solution) of wet portion 151 into the dryportion 152 prior to activation of the automatic injection assembly.Generally, seal structure 160 can include an outer sealing member 180, amovable sealing plug 166, a by-pass zone 165, at least one flow path167, and preferably also includes a filter or membrane 164. Withreference to FIG. 5A-D, seal structure 160 can preferably be formed as asix piece (FIG. 5A), five piece (FIG. 5B), four piece (FIG. 5C), orthree piece (FIG. 5D) configuration.

More particularly, with reference to FIG. 5A, the outer sealingstructure 180 of the six piece configuration can comprise a two pieceannular rigid body 181 wherein members 181 a, 181 b thereof are formedinto the two piece rigid body using, e.g., annular weld connections orother bonding techniques known in the art. Outer sealing structure 180can further include multiple external sealing members 182, e.g., twoO-rings, to provide an annular sealing engagement with the inner wall ofvial or compartment 150. The sealing structure 180 further includes aninternal plug member 166 and a filter or dispersion membrane 164 as willbe discussed in greater detail later.

In another embodiment, as shown in FIG. 5B, rather than plural O-rings,outer sealing structure 180 can include a single external sealing member182, e.g., a unitary gasket, to provide an annular sealing engagementwith the inner wall of vial or compartment 150. External sealing member182 may optionally be secured to two piece rigid body 181 using anybonding techniques known in the art. Further, rigid body members 181 a,181 b may be shaped such that they securingly engage external sealingmembers 182 within notched recesses 183. Alternately, sealing members182 may be secured to rigid body members 181 a, 181 b by an interferencefit. As with the first embodiment, a filter or membrane 164 is clampedin place at the proximal end of flow path 167 between member 181 a andmember 181 b of the two piece rigid body.

In another embodiment, as shown in FIG. 5C, outer sealing structure 180comprises a unitary internal rigid member 181 and an external sealingmember 182. Again, internal rigid member 181 and external sealing member182 may optionally be secured together using any bonding techniquesknown in the art. Further, internal rigid member 181 and externalsealing member 182 may be formed such that they securingly engage eachother using a combination of notched recesses 183 and extendingshoulders 184. The filter or membrane 164 can be held in place betweeninternal rigid member 181 and shoulder 184 of external sealing member182. Alternatively, the filter 164 may be ultrasonically welded orotherwise secured to the rigid member 181. In yet another embodiment, asshown in FIG. 5D, outer sealing object 180 can comprise a unitaryexternal sealing member 182 which can optionally be molded so as toaccommodate filter or member 164 within retaining recess 185. FIGS. 6Aand 6B illustrate another embodiment that is very similar to that ofFIG. 5A, but provides a slightly different shape for outer annular rigidbody 181 and particularly the members 181 a, 181 b thereof.

In each embodiment illustrated in FIGS. 5A-5D and 6A-6B, externalsealing member 182 is preferably formed from a non-reactive elastomermaterial which can provide for the necessary sealing engagement with theinner wall of vial or compartment 150. Further, external sealing member182 can optionally be lubricated with silicon or other suitablenon-reaction lubricant to facilitate movement of the outer sealingobject 180 forwardly within vial or compartment 150 upon receivingsufficient force as will be described. The movable sealing plug 166 ispreferably formed from a material, such as an elastomer or PTFE, havinglow frictional properties such that the sealing plug 166 may easilyslide within outer sealing object 180 when the injector is activated.The movable sealing plug 166 may also optionally be lubricated withsilicon or other suitable non-reactive lubricant. In the embodimentsillustrated, and as specifically shown in FIG. 6B, it is preferred thatthe outer annular structure 180 defines an inner surface having a smoothcylindrical configuration towards the rearward portion 169 thereof, andlongitudinally extending grooves 168 towards the forward portionthereof. The grooves 168 create a flowpath or flowpaths 167 throughwhich liquid in the wet compartment 151 can bypass seal plug 166 whenthe plug 166 is moved forwardly from sealing engagement with cylindricalsurface portion 169 into the grooved portion 168. The movement of thesealing plug 166 into the by-pass area 165 opens the fluid flow path 167between wet portion 151 and dry portion 152. The movable sealing plug166 preferably includes a plurality of circumferential grooves 186 toprovide for enhanced sealing engagement and to facilitate sliding actionof the plug 166.

As mentioned above, the seal structure 160 preferably includes filter ormembrane 164 at the end of flow path 167 through which the liquidinjection solution may pass after the injector has been activated. Theliquid injection solution then enters the dry portion 152 of the chamber150 where it mixes with and dissolves the dry medicament. Moreparticularly, the filter 164 disperses the liquid injection solutionexiting the seal structure 160 to present laminar fluid flow to the fullsurface of the dry medicament, thereby wetting the entire surface of thedry medicament for rapid and complete dissolution. The filter membrane164 can be any structure that generally uniformly distributes the liquidacross the entire diameter of the chamber 150 for enhanced dissolutionof the dry medicament.

During operation, manual activation of the actuator assembly 120releases the collet 122 (as described above), which applies pressure onthe plunger assembly 170. The application of pressure on the plungerassembly 170 by the collet and spring assembly 124 moves the plunger 170in the direction of the needle assembly 140. As a result, the entirechamber 150 and needle assembly 140 are moved forwardly in the housing110 such that needle 141 pierces through the front end of sheath 202 andexits through the forward end of the housing 110, and particularlythrough a hole 204 in the front nose-cone portion 206 of the housing.The sheath 202, which serves to maintain the needle 141 sterile when theinjector is in storage, also serves as a shock absorber duringactivation as it is compressed in generally accordion like fashionbetween the nose cone 206 and needle support 143.

When the needle 141 is extended from the housing 110 and the chamber 150and needle support 143 approach the nose cone 206 portion of the housingso that further forward movement of chamber 150 is substantiallyresisted, the plunger 170 then begins to travel forwardly through thechamber 150. This pressurizes the liquid injection solution locatedwithin the wet compartment 151. With reference to FIG. 6A-6B, theincreased pressure within the wet compartment 151 moves the sealing plug166 from a first sealed position wherein sealing plug 166 is sealinglyengaged with surface 169 of outer sealing structure 180 (FIG. 6A) to asecond by-pass position (FIG. 6B) that allows the injection solution toflow through flow path 167 created by grooves 168 and thereby throughseal structure 160.

As described above, the high pressure developed within the wet portion151 in response to movement of the collet 122 and the plunger assembly170 forces the liquid injection solution through the seal structure 160dissolving the drug into a medicament injection solution which will thenbe forced out through the needle 141 and into the patient. As the collet122 and plunger assembly 170 continue forward, the plunger 170 willeventually contact the seal structure 160, which, in a preferredembodiment, causes the seal structure 160 to move in the direction ofthe needle assembly 140. Movement of the seal structure 160 would causeany remaining solution within the portion 152 to be dispersed throughthe needle assembly 140, so as to reduce the amount of residualmedicament remaining within the chamber 150.

As shown in FIGS. 2A, 2B and 4, a membrane or filter 190 is preferablyprovided adjacent the needle assembly 140 to prevent any dry medicamentparticles from clogging the rearward end of needle 141 prior to aninjection operation. The membrane 190 may also serve to slightlyrestrict or slow injection of medicament into the patient, to facilitatemore thorough dissolution during injection.

More particularly, to prevent the passage of undissolved dry medicamentto the needle assembly 140, a medicament support 190 is preferablyprovided between the end of the dry compartment 152 and the needleassembly 140. The support 190 can serve to prevent blockage of theneedle assembly 141 by preventing the dry medicament from entering thearea surrounding the needle assembly 140 while permitting passage of themixture of dissolved medicament and liquid injection solution. Thesupport 190 may be configured as described in U.S. ProvisionalApplication No. 60/238,448, which is herein incorporated by reference ina manner consistent with this disclosure. It is contemplated thatmultiple supports 190 may be located within the dry compartment 152. Theprovision of the supports 190 may also improve the laminar flow of theliquid injection solution through the dry medicament thereby improvingdissolution.

Further, a diaphragm assembly (not shown) may also be provided adjacentthe medicament support 190, as known in the art. The diaphragm assemblyacts to prevent the passage of the liquid injection solution to theneedle assembly 140 prior to activation of the actuator assembly 120.More particularly, the diaphragm assembly will not rupture until eitherthe butt end of the needle assembly 140 ruptures the expanded diaphragmor sufficient pressure builds in the dry compartment 160 to rupture thediaphragm, again as known in the art.

As described above, the movement of the collet 122 causes the injectionneedle 141 of the injection assembly 140 to advance and protrude throughthe housing 110. As such, the injection of the medicament can beperformed with a simple operation. In sum, the user simply removes theend cap assembly 130, locates the injection end of the housing 110adjacent the injection site, and presses the push button 132. Thisoperation automatically triggers the operation of the drive assembly orspring 250 to advance the collet 122 causing the liquid injectionsolution located within the wet portion 151 to enter the dry portion 152through the seal structure 160. The dissolved medicament is thentransmitted through the injection needle 141 to provide the user withthe necessary dose of medicament. The automatic injector 10 inaccordance with the present invention reduces the amount of timerequired to administer medicament compared to other wet/dry injectorsand eliminates the need for mixing by the user.

The seal structure 160 advantageously enables the manufacture of asuperior wet/dry auto injector with a complementary combination ofcomponents that are either known in the art of conventionalauto-injectors or are otherwise relatively simple to manufacture. Theseal structure 160 enables sufficient mixing of wet and dry medicamentcomponents without requiring manual shaking. This mixing action isenhanced by the filter or membrane 164. In a preferred embodiment, thefilter 164 is a supported, hydrophobic acrylic copolymer cast on anon-woven nylon support. Preferably, it is a FlouRepel treated membranefor superior oleophobicity/hydro-phobicity.

In another embodiment, shown in FIG. 7, the automatic injector cartridgeincludes a needle assembly 140 located within the dry portion 152. Theneedle assembly 140 extends within the dry portion 152 to the sealingstructure 180, described above in connection with FIGS. 5A-5D. Thesealing structure 180 separates the dry portion 152 from the wet portion151. As shown in FIG. 7, the cartridge further includes a plunger 170positioned therein. The plunger 170 is configured to engage the collet122 of the activation assembly 120. The cartridge includes a sheath 301.Like the sheath 202, the sheath 301 maintains the needle 141 in asterile environment until it projects from the end of the sheath 301 inresponse to activation of the activation assembly 120. During operation,the needle assembly 140 passes through the dry portion 152 as the wetmedicament passes through the sealing structure 180.

In other embodiments (see FIGS. 8A and 8B), no inner plug 166 isprovided. Rather, the outer structure 180 is simply complemented by aseal membrane 226 that extends across the inner area defined by theinner surface of the outer structure. When the chamber 150 reaches theforward end of the housing during an injection operation, pressurizationof the wet compartment 151 causes the seal membrane 226 to rupture,thereby allowing the seal structure 160 to permit liquid to passtherethrough. In this embodiment, it may be desirable to provide theseal structure 160 with a pointed member 228 disposed adjacent to theseal membrane 226 to facilitate rupturing of the seal membrane uponpressurized expansion thereof during an injection operation. The member232 on which the pointed member 228 is mounted has a plurality ofpassages 234 that permits fluid to pass therethrough. Filter or membrane164 is preferably mounted distal to the passages 234 to present laminaror distributed flow to the dry medicament.

EXAMPLES

An injector according to the present invention was loaded with liquidinjection solution and dry medicament and activated with the followresults. Loaded Dispensed Operational Dry Powder Fluid Dry Powder FluidTime Mg Ml % mg ml Secs. 531 2.7 94 497 2.3 4.0 557 2.7 93 515 2.3 4.5582 2.6 92 537 2.2 4.4

Other embodiments and modifications of the invention are alsocontemplated. For example, a cover assembly, described for example inU.S. Pat. No. 5,295,965 (the disclosure of which is specificallyincorporated herein by reference) may be secured to the injection end ofthe housing 110 after deployment of the medicament. Furthermore, theautomatic injector may further include a nipple plunger assembly, asdescribed for example in U.S. Pat. No. 5,713,866 (the disclosure ofwhich is specifically incorporated herein by reference).

In yet a further embodiment, the forward dry chamber 152 contains theneedle 141, as shown in FIG. 7. The needle 141 is forced through aforward plug stopper upon initial compression of the two chamber system.As known in the art, providing the needle 141 in the forward chamber 152provides improved longitudinal compactness of the design.

In yet another embodiment, a pre-filled syringe is provided with theseal structure disposed between wet and dry components.

In further contemplated embodiments, the seal structure 160 can be usedin the same type of injector described herein, except rather thanemploying a dry (powder) medicament separated by a liquid component, afirst liquid medicament is separated from a second fluid component bythe seal structure 160. In yet another embodiment, the seal structure160 can be used in what is known in the art as a “needleless injector”where an injection can be made into a patient without a needle orcannula.

FIG. 9 is a longitudinal cross-sectional view of a chamber 350 mountedto a needle assembly 340 according to a further embodiment of theinvention. Neither a housing 110 nor an actuator assembly 120 is shownin FIG. 9; however, the chamber 350 and needle assembly 340 may be usedwith the housings 110 and actuator assemblies 120 described above orwith substantially any known housing or actuator assembly.

In the chamber 350 and needle assembly 340 shown in FIG. 9, many of thecomponents are the same as those described above with respect to FIG. 1;therefore, the description above will suffice for those components.

Like the chamber 150, the chamber 350 has a wet portion or compartment151 and a dry portion or compartment 152. A sealing structure 360separates the wet portion 151 and the dry portion 152. The sealingstructure 360 includes an outer sealing member 380, a moveable sealingplug 166, a by-pass zone 165, and may also include a filter ordispersion membrane 164. Although a moveable sealing plug 166 is shownin FIG. 9, the sealing structure 360 may include a rupturable sealmembrane 226 instead of a sealing plug 166, as shown in FIGS. 8A and 8B.

FIG. 10 is a perspective view of the outer sealing member 380. FIG. 11is a front elevational view of the sealing member 380, and FIG. 12 is asectional view of the outer sealing member 380 taken through Line 12-12of FIG. 11. As shown, the outer sealing member 380 has an annular wiperportion 382 that makes sealing contact with the inner wall of the dryportion 152 of the chamber 350 and extends axially forwardly, in thedirection of actuating movement along the longitudinal axis of thechamber 350, toward the needle assembly 140.

While the outer sealing members 180 that were described above do form aseal with the inner wall of the container 150, during the actuationprocess, powder from the dry medicament in the dry portion 152 tends toaccumulate around the sealing member 180, 380 at the seal/containerinterface. As the device actuates, some of the powder that accumulatesaround the sealing member 180, 380 can be driven or forced into thespace between the glass and the sealing member 180. The entire areaaround and between the sealing member 180 and the inner wall of thecontainer 150 can become a “dead space,” in which accumulated powdercannot properly mix with fluid.

The wiper portion 382 helps to eliminate the accumulation of powderaround the sealing member 380 by “wiping” or “scraping” any accumulatedpowder away from the wall of the chamber 350 and directing it radiallyinwardly, where it can properly mix with the wet medicament portion asthe sealing member 380 passes through the dry portion 152. As shown inFIG. 9, the wiper portion 382 makes contact with the inner wall of thedry portion 152 of the chamber 350 along substantially the entirety ofits length. The extent of contact between the wiper portion 382 and theinner wall of the dry portion 152 is possible, at least in part, becausethe wiper portion 382 extends axially. Although it would be possible toconstruct a wiping structure that extended radially or angularly outwardfrom the main body of the sealing member 380, such a wiping structurewould not be in contact with the inner wall of the dry portion 152 oversubstantially the entirety of its length. Therefore, it would bepossible for such a putative wiping structure to cause an undesirableaccumulation of medicament powder, particularly if medicament powderwere to move past it and into the space between it and the inner wall ofthe dry portion 152. Accordingly, the straight, forwardly-extendingwiper portion 382 is currently preferred.

A wiper portion 382, although shown in the embodiment of FIG. 9, may beused in any of the embodiments shown and described above and in anyvariations thereof.

As shown in FIG. 9, the chamber 350 has an “open mouth” configuration;i.e., the container itself does not taper substantially as it meets theneedle assembly 340 (for example, as compared with the embodiment shownin FIG. 3A). The advantages of having an “open mouth” container weredescribed above with respect to the container 150. If the “mouth” of thecontainer (i.e., the opening into the dry portion 152 of the container)is open and wide, it becomes easier to load the dry component of themedicament. However, having a tapered portion adjacent to the needleassembly 340 helps to direct the medicament radially inwardly, towardthe needle assembly 340, when the injection is taking place.

In order to realize the advantages of an “open mouth” container and theadvantages of a tapered container, the chamber 350 includes a taperedinsert 384 at its mouth, just behind the needle assembly 340. FIG. 13 isa perspective view of the tapered insert 384, FIG. 14 is a frontelevational view, and FIG. 15 is a sectional view through Line 15-15 ofFIG. 14.

The tapered insert 384 tapers radially inwardly as it extends axiallyforwardly, such that it forms a funnel portion 386 with a small centralopening 388 at one end. The tapered insert 384 also has a rearward openend 389 with a larger open diameter. The insert 384 sealingly engagesthe walls of the chamber 350. Extending radially outward from the outersurface of the funnel portion 386 proximate to the small central opening388 is an annular sealing flange 390. In the embodiment shown in FIGS.13-15, the annular sealing flange 390 is an integral portion of thetapered insert 384. However, in some embodiments, the annular sealingflange 390 may be joined to the funnel portion 386 by adhesives or othersecuring methods. Additionally, as will be described in more detailbelow, in some configurations, the annular sealing flange 390 may beabsent. The insert 384 is preferably formed from a material that willnot react with the dry medicament stored in the compartment 152.

The chamber 350 and needle assembly 340 include a metallic skirt,generally indicated at 392, that is rolled or crimped so as to captureor secure the needle assembly 340 to the front end of the chamber 350.In this embodiment, the annular sealing flange 390 fits between thechamber 350 and needle assembly 340 so as to form a seal between them.Either the annular sealing flange 390 itself or, depending on theconfiguration, the entire tapered insert 384 may be made of anelastomeric or other rubber material suitable for sealing.

The tapered insert 384 may be removed from the chamber 350 in order toeffect the loading of the dry medicament and then inserted into thechamber 350 prior to joining with the needle assembly 340. Although thetapered insert 384 is shown with a funnel portion 386 of constant,radially inward taper, the tapering of the tapered insert 384 may be ofany type that will facilitate fluid flow from the chamber 350 into theneedle assembly 340.

At the forward end of the tapered insert 384, the small, central opening388 in the insert 384 is covered by a filter 190 that is positionedbetween the tapered insert 384 and the needle support 343 to filterfluids passing from the chamber 350 into the needle assembly 340, so asto prevent any undissolved medicament from entering the needle assembly340. Forward of the filter 190, defined by the rearward(container-facing) side of the needle support 343 is a chamber 394 thattapers radially inwardly toward its forward end. The chamber 394 iscontoured to expose a substantial portion of the surface area of thefilter 190 to the flow between the chamber 350 and the needle assembly340. Preferably, the chamber 394 has an opening at least as large as thesmall central opening 388 in the tapered insert 384. In the embodimentshown in FIG. 9, the chamber 394 is substantially hemispherical,although other configurations may be used. The chamber 394 can be seenmore clearly in FIG. 16, which is a longitudinal cross-sectional view ofa portion of the needle assembly 340. The chamber 394 allows greater,more laminar, and more fully developed flow through the filter 190 tothe needle 141. Furthermore, the chamber 394 is shaped to direct theflow of medicament to the needle 141.

As is also shown in FIG. 16, neither the needle 141 nor any otherstructure protrudes into the chamber 394. Although it would be possibleto construct a chamber 394 and needle assembly such that a portion ofthe end of the needle protruded into the chamber 394, such anarrangement might cause turbulent flow around the end of the needle thatprotruded into the chamber 394, or might otherwise eliminate some of thebenefits of the chamber 394.

The sealing member 380 with wiper portion 382, tapered insert 384, andchamber 394 may all be used in a wet/wet autoinjector assembly thatincludes two fluid medicament components. In a wet/wet autoinjectorassembly, a burstable membrane is typically positioned over the openingof the compartment adjacent to the needle assembly, in order to preventfluid in that compartment from leaking out of the compartment and intothe needle assembly. If the sealing member 380, tapered insert 384, andchamber 394 are provided in a wet/wet autoinjector assembly, a burstablemembrane may be provided as a portion of the tapered insert 384. Forexample, the burstable membrane could be positioned in the funnelportion 386 of the insert.

The sealing member 380, tapered insert 384, and chamber 394 may also beused in a wet/dry or wet/wet autoinjector assembly that does not includeall of the features described above. For example, the tapered insert 384and chamber 394 may be used in any wet/dry or wet/wet autoinjector inorder to improve the loading and dispensing performance of theautoinjector.

A chamber for an autoinjector may be filled with appropriate medicamentcomponents in several different ways. For example, one common way tofill an autoinjector chamber is to fill a first medicament (e.g., a wetmedicament) through an opening in the chamber and then fill a secondmedicament (e.g., a dry medicament) through that same opening in thechamber. This process, while common, tends to cause cross-contaminationbecause both wet and dry medicaments are filled through the sameopening. For example, if a dry powder medicament is filled first, anypowder that accumulates around the opening may mix with asubsequently-filled wet medicament, thereby contaminating the contentsof the wet compartment. Conversely, if the wet medicament is filledfirst, liquid that accumulates around the opening may mix with some ofthe subsequently-filled dry medicament, thereby contaminating thecontents of the dry compartment.

However, using a chamber 150, 350 according to the invention, it isadvantageous to fill the chamber 150, 350 using a separate opening inthe chamber 150, 350 for each type of medicament, thus eliminating thecross-contamination problem. This sort of filling process for a chamber150, 350 includes a number of tasks and will be described below withrespect to the chamber 350, although the described process is, ingeneral, equally applicable to the other embodiments described above.Ordinarily, the filling process would be performed in an asepticenvironment.

Typically, the chamber 350 is initially open at both ends and does notinclude any interior structures, as shown in FIG. 17A. A seal structure,such as seal structure 360, is first inserted into the chamber 350 sothat it is positioned substantially as shown in FIG. 17B.

Once the seal structure 360 is in place, the chamber 350 is removed toor placed in a low particulate aseptic environment, and is positioned sothat the wet portion or compartment 151 can be filled through an opening396 in the rear end of the chamber 350, as shown in FIG. 17C. (The lowparticulate environment prevents possible cross-contamination of the wetportion 151.) After the wet portion 151 is filled, the opening 396 inthe rear end of the chamber 350 is sealed by installing the plunger 170,as shown in FIG. 17D. The placement of the chamber 350 in a lowparticulate environment prior to filling the wet portion 151 helps toprevent contamination of the wet portion 151 by powder or otherparticulates.

Once the wet portion 151 is filled with the desired liquid medicamentportion and the rear end is sealed with the plunger 170, the chamber 350is removed from the low particulate environment and is placed in anappropriate aseptic environment so that the dry portion or chamber 152of the chamber 350 can be filled through an opening 398 in the front ofthe chamber 350. There are two common ways of filling the dry portion152. One way to fill the dry portion 152 is to place a dry powderdirectly into the dry portion 152 through the opening 398, as shown inFIG. 17E.

Another way to fill the dry portion 152 is to fill the dry portion 152with a liquid medicament through the opening 398 and then lyophilize theliquid medicament directly in the dry portion 152 to leave only thedesired dry medicament. While this process of liquid filling andlyophilizing may be used, it sometimes leaves residues in the dryportion 152, which may interfere with the stability of the drymedicament or otherwise contaminate it.

A third way to fill the dry portion 152 is to lyophilize a liquidmedicament in a separate container to form a lyophilized dry medicamenttablet 400 and then deposit the dry medicament tablet 400 in the dryportion 152 through the opening 398, as shown in FIG. 17F. Thisvariation of the filling process is used most advantageously with achamber that has a relatively wide opening into its dry portion, so thattablets of various sizes can be accommodated. If a chamber has arelatively narrow opening into its dry portion, it may be necessary tofill that dry portion with powder, or to lyophilize a liquid medicamentdirectly in the dry portion to form a dry powder.

After the dry portion 152 is filled, a tapered insert 384 is placed inopening 398 of the chamber 350 and the needle assembly 340 is securedover the tapered insert 384. When the process is complete, the chamber350 is as shown in FIG. 9.

Although the present invention has been described with respect to anumber of embodiments, those embodiments are meant to be illustrative,rather than limiting. As those of ordinary skill in the art willunderstand, modifications and variations are possible within the scopeof the appended claims.

1. An automatic injection device containing a pre-loaded charge ofmedicament for automatically self-administering the medicament uponactuation thereof, the device comprising: a housing; a medicamentchamber disposed in the housing, the medicament chamber including afirst compartment containing a dry medicament portion, and a secondcompartment containing a wet medicament portion to be mixed with the drymedicament portion; a seal structure between the first compartment andthe second compartment, the seal structure being initially in a sealingcondition that maintains the first compartment separate from the secondcompartment, the seal structure including: at least one flow path formedtherein, and an annular wiper portion disposed at the front end of theseal structure and positioned to engage inner walls of the firstcompartment as the seal structure is moved through said firstcompartment, said wiper portion being configured to direct drymedicament particles engaged with the inner walls radially inwardly asthe seal structure moves through the first compartment, the sealstructure being converted to a mixing condition as a result ofactivation of the device; a needle assembly that dispenses the mixedmedicament portions from the medicament chamber; and an activationassembly carried by the housing and including a stored energy source,wherein activation of the activation assembly releases the stored energyfrom the stored energy source, causing the seal structure to beconverted from the sealing condition to the mixing condition, andthereby causing or allowing the medicament portions to be mixed andforced through the needle assembly.
 2. The automatic injection device ofclaim 1, wherein the first compartment is adjacent the needle assemblyand disposed forwardly of the second compartment.
 3. The automaticinjection device of claim 1, further comprising an insert mounted in theforward end of the chamber adjacent the needle assembly, the insertdefining a tapering flow pathway that tapers radially inwardly as itextends axially forward.
 4. The automatic injection device of claim 3,further comprising a filter positioned between the medicament chamberand the needle assembly.
 5. The automatic injection device of claim 4,wherein the needle assembly comprises a needle support for mounting theneedle assembly to a front end of the medicament chamber, the needlesupport defining a chamber provided adjacent to the filter on a needleassembly side of the filter.
 6. The automatic injection device of claim5, wherein the needle support chamber adjacent to the filter has anenlarged rearward end opening of a size that is at least as large as afront end opening of the insert.
 7. The automatic injection device ofclaim 6, wherein the needle support chamber adjacent to the filter has asubstantially hemispherical shape.
 8. The automatic injection device ofclaim 7, further comprising a fluid distributing member disposed betweenthe first compartment and the second compartment.
 9. The automaticinjection device of claim 8, wherein the fluid distributing member is afilter.
 10. The automatic injection device of claim 1, wherein the sealstructure comprises an outer seal structure carrying the wiper portion,the flow path being formed in the outer seal structure, and a plugmember for sealing the flow path when the seal structure is in thesealing condition.
 11. The automatic injection device of claim 10,wherein the seal structure has an outer periphery that forms aperipheral seal with an interior wall of the medicament chamber, andwherein said plug member is spaced radially inward from the peripheralseal that seals the at least one flow path formed in the seal structure.12. The automatic injection device of claim 1, wherein the wiper portioncomprises a peripheral lip having an inner surface that extends radiallyinwardly as it extends axially rearward.
 13. An automatic injectiondevice containing a pre-loaded charge of medicament for automaticallyadministering the medicament upon actuation thereof, the devicecomprising: a housing; a chamber disposed in the housing, the chamberhaving a first compartment containing a dry medicament portion, and asecond compartment containing a wet medicament portion to be mixed withthe dry medicament portion; a seal structure between the firstcompartment and the second compartment, the seal structure initially ina sealed condition to maintain the first compartment separate from thesecond compartment, the seal structure converting to a mixing conditionin response to activation of the device, the seal structure including:an outer sealing member that forms a peripheral seal with an interiorwall of the chamber, a movable sealing plug spaced radially inward fromthe outer sealing member, the sealing plug in a first position when theseal structure is in the sealed condition and in a second position whenthe seal structure is in the mixing condition, a filter or dispersionmembrane, and at least one flow path between the sealing plug and thedispersion membrane; a needle assembly that dispenses the mixedmedicament portions from the chamber; and an activation assemblydisposed in the housing and including a stored energy source, whereinactivation of the activation assembly releases the stored energy fromthe stored energy source causing the seal structure to convert from thesealed condition to the mixing condition, wherein the medicamentportions are mixed and forced through the needle assembly.
 14. Theautomatic injection device of claim 13, wherein the seal structurefurther comprises an annular wiper portion disposed at the front end ofthe outer sealing member, the wiper portion positioned to engage aninterior wall of the first compartment as the seal structure is movedthrough the first compartment, the wiper portion configured to directdry medicament particles engaged with the interior wall radially inwardas the seal structure moves through the first compartment when in themixing condition.
 15. The automatic injection device of claim 14,wherein the annular wiper portion comprises a peripheral lip having aninner surface that extends radially inward as it extends axiallyrearward.
 16. The automatic injection device of claim 13, wherein theouter sealing member comprises an O-ring that provides an annular sealwith the interior wall of the chamber.
 17. The automatic injectiondevice of claim 13, wherein the seal structure further comprises aby-pass zone between the movable plug in the sealed condition and thedispersion filter or membrane.
 18. The automatic injection device ofclaim 13, wherein the dispersion filter or membrane comprises ahydrophobic acrylic copolymer cast on a non-woven nylon support.
 19. Anautomatic injection device containing a pre-loaded charge of medicamentfor automatically administering the medicament upon actuation thereof,the device comprising: a housing; a chamber disposed in the housing, thechamber having a first compartment containing a dry medicament portion,and a second compartment containing a wet medicament portion to be mixedwith the dry medicament portion; a seal structure between the firstcompartment and the second compartment, the seal structure initially ina sealed condition to maintain the first compartment separate from thesecond compartment, the seal structure including: an outer sealingmember that forms a peripheral seal with an interior wall of thechamber, a seal membrane extending across the inner area defined by theinner surface of the outer sealing member, the seal membrane operativeto rupture upon pressurization of the second compartment, a dispersionfilter or membrane, and at least one flow path between the seal anddispersion membranes; a needle assembly that dispenses the mixedmedicament portions from the chamber; and an activation assemblydisposed in the housing and including a stored energy source, whereinactivation of the activation assembly releases the stored energy fromthe stored energy source causing the second compartment to pressurizeand the seal membrane to rupture, wherein the medicament portions aremixed and forced through the needle assembly.
 20. The automaticinjection device of claim 19, wherein the seal structure furthercomprises a pointed member disposed adjacent the seal membrane tofacilitate rupturing of the seal membrane upon pressurization of thesecond compartment.